Intense interest has centred on the need for development of novel immunosuppressant agents and/or regimens which might have clinical utility in disorders including autoimmunity, allergy and transplantation (1). Given the evidence that efficient induction of T cell immunity depends upon the existence of accessory signals provided by a variety of costimulatory molecules (and their natural ligands) (2–6) it had been hoped that systematic blockade of such costimulation might provide the immunosuppression required. In general however, results of trial, both in experimental animals and man, on the use of these reagents alone, or even in combination, have not provided evidence for consistent inhibition of immunity (7–9). More recent studies have begun to characterize receptor:ligand molecules which deliver regulatory (suppressive signals) directly to antigen activated T cells (10–14). Note that, at least for CTLA4, there is evidence that the same molecule may deliver either positive or negative costimulatory signals, according to the overall molecular milieu in which T cell activation occurs (15, 16).
The inventor has characterized another ligand:receptor pair, CD200:CD200R, which he has implicated in the direct delivery of suppressive responses after antigen challenge (14, 17). Treatment of animals with foreign allo- or xeno-grafts, or immunized with bovine collagen, with a soluble form of CD200 (CD200Fc) prevents graft rejection or development of collagen-induced arthritis (CIA) respectively (18). Similar effects are observed after infusion of a cross-linking anti-CD200R (19). Supporting evidence for a role for CD200:CD200R interactions in regulation of inflammation/autoimmunity comes from work of Hoek et al, who recently described some of the phenotypic properties of CD200 KO mice (20). These animals showed increased susceptibility to both CIA and experimental allergic encephalomyelitis, an animal model of multiple sclerosis, along with evidence for increased proliferation of CD200R+ cells. These data have suggested a physiological role for CD200 in the regulation of activation of CD200R+ cells of the monocyte/myeloid lineage, which are presumably in turn responsible for inflammation in these conditions. The inventor has also provided evidence for expression of CD200R on cells of T lymphocyte origin (17), and hypothesize that CD200 might exert a more direct role on T cell activation (22).
It would be useful to have an animal in which inducible overexpression of CD200 can be achieved in order to study the role of CD200 in various diseases.